(Section A: Virology) Lecture 05: Virus Entry Flashcards
State:
Concept of Virus Entry
- Recognition of host receptor (attachment)
- Mechanism to release genome (eg. in the cytoplasm)
True or False:
Viruses can passively diffuse through the cell membrane
False, they are too large to be passively transported through the host cell membrane
KEY CONCEPT:
The virion must be….
Stable and unstable
* Varies during different times of infectious cycle
Do random electrostatic interactions by the virus with host cells initiate infectious cycle?
No
What do interactions with the receptor allow a virus to do?
“Opens the door” for the virus, allows virus to release genome inside host
True or False:
Host cell receptors recognize viruses
True
Define:
Co-receptor
Sometimes viruses require a second receptor in order to enter a host cell
There are a variety of host cell receptors, what are characteristics shared by all of them?
- All are surface membrane proteins
- Same receptor can recognize more than 1 virus
Define:
PVR
Polio virus receptor
Define:
ACE2
Angiotensin-Converting Enzyme 2 receptor
* SARS CoV2 receptor
Define:
CD46
Cell viral receptor for Measles Virus
Define:
LDL Receptor
Host cell viral receptor for Rhinoviruses (common cold etc.)
Why are there two different modes of attachment for viruses?
Viruses can be non-enveloped hard shell virus or enveloped virus
Describe:
Entry for a non-enveloped virus with icosahedral symmetry
(use a virus for example)
Picornaviridae - Poliovirus
* ssRNA (+) virus, ready-to-go
* Has viral proteins 1, 2, 3
Steps:
* VP1 interacts with PVR
* At least 2 interactions at a time
* Interacts directly with the plasma membrane
* Creates conformation change
* Hydrophobic N-termini of VP1 insert into membrane, results channel for genome entry
Describe:
Entry for an enveloped virus
(use a virus for example)
Influenza virus
* ssRNA (-), has to make RNA (+)
* Has hemagglutinin
Heamgglutinin binds to host cell receptors
* Interacts with Sialic Acid
Describe:
Sialic acid mechanism
Sialic acid attaches to galactose, resulting in two possible forms:
* 2-3 carbon linkage (mostly in upper respiratory tract)
* 2-6 carbon linkage (mostly in lower respiratory tract)
Compare:
Human influenza and Avian influenza
(in terms of virus entry)
Human influenza
* Prefer 2-6 linkages
* Infects upper respiratory tract
Avian influenza
* Prefer 2-3 linkages
* Infects lower respiratory tract (lungs)
Early CoV2 infected lower respiratory tract. What are trademarks of this?
Slow appearance of symptoms (takes long time for virus to get in and replicate)
* Severe symptoms
Omicron variants of CoV2 infected the upper respiratory tract. What was a trademark of this?
Quick appearance of symptoms
* Not severe, as it only infects upper respiratory tract
* More infectious
Virus enter the cell via…
Common cellular mechanisms
What are some common cellular mechanisms for entry?
- Phagocytosis
- Pinocytosis
- Receptor-mediated endocytosis
What are the 3 forms of cellular entry mechanisms we study known as?
Endocytosis (happens at surface of cell)
True or False:
Endocytosis is passive transport
False, it is active transport
Give an analogy for:
Cell entrance mechanisms
Transport vesicles “move” along tracks that are powered by molecular motors
Define:
Release
A trigger that releases virus or genomic contents in the cytoplasm
Where can genomic “release” occur?
- Right at the cell surface
- Early endosome
- Late endosome
State:
pH of different locations of release
- Cell surface: 7.0 pH
- EE: 6.5-6.0 pH
- LE: 5.5-5.0 pH
Describe:
Reovirus entry
Has a hard shell, dsDNA
* Like an “onion”, multilayered
- pH at EE causes loss of capsid
- Cystein proteases at LE begin to cut into the virus
- Virus is ready to release genome
What are cystein proteases? Are they host or virus?
Cathepsins
* They are host cell proteins
* Active in late endosome
Describe:
Paramyxoviridae (Measles virus) entry
Enveloped virus
* Goes through fusion events
Viral proteins mediate fusion events
* Behave differently depending on the specific pH
Describe:
Viral fusion event
(use influenza virus example)
- Proteins are originally packed down
- Gets protonated, causes viral proteins to “stretch out”
- Links to host cell membrane
- Pulls in the membrane and creates channel for genome to enter
What is unique about Ebola virus?
Ebola virus performs fusion event that is pH dependent
Injects genome at late endosome
* Attaches to NPC1 receptor (lipid transporter)
* A sugar blocks viral receptor (GP1/GP2)
* When eliminated by cathepsins, allows ebola virus to attach to NPC1 and enter
True or False:
NPC1 is a cell surface receptor
False, it is a late endosome receptor
